Patent EP-0076528-A2 (EP)
Inventor: HEYMES RENE
IPC: C07D501/34
Filed: 1981-02-13
Abstract: 1. Claims for the Contracting States : BE CH DE GB IT LI LU NL SE Products of general formula (A') :  see diagramm : EP0076528,P43,F2 syn isomer in which R'1 , R", n, A, X', and R'a have the following significance either A] A represents a hydrogen atom, an equivalent of an alkali metal, of an alkaline-earth metal, of magnesium, of ammonium or of an aminated organic base or A represents the remainder of an ester group that can be easily cleaved, R'a represents an alkyl radical optionally interrupted by a heteroatom, linear or branched alkenyl or alkynyl radical having at most 6 carbon atoms or a benzyl or phenylethyl radical optionally substituted by a carboxy, amino or dimethylaminoethyl radical, n is equal to 0, 1 or 2, X' represents a sulphur atom optionally oxidised in the form of sulphoxide or sulphone or an oxygen atom and R" and R'1 are such that either R'1 represents a protector group of the amino radical and R" represents R', R' represents a hydrogen atom, a protector group of the hydroxyl radical, a linear or branched alkyl radical, alkenyl, alkynyl or cycloalkyl radical having at most 6 carbon atoms, or R' represents an acetyl, propionyl, buturyl, valeryl, hexanoyl, acryloyl, crotonoyl, benzoyl or carbamoyl radical, each of these radicals being optionally substituted by one or more radicals chosen from among the following radicals, carboxy optionally salified or esterified, methoxycarbonyl, ethoxycarbonyl, carbamoyl, dimethylcarbamoyl, amino methylamino, dimethylamino, halogen, methoxy, ethoxy, propyloxy, methylthio, ethylthiophenyl, tetrazolyl, phenylthio, tetrazolylthio or thiadiazolylthio optionally substituted by methyl or R' represents an alkoxy carbonyl radical, or R'1 represents a hydrogen atom and R" represents a protector group for the hydroxyl radical chosen from the following radicals, phenoxyacetyl, benzoylformyl, p-nitro benzoyl, propoxycarbonyl, beta-beta-beta-trichloroethoxycarbonyl, benzyloxycarbonyl, tert-butoxycarbonyl, 1-cyclopropylethoxycarbonyl, tetrahydropyrannyl, tetrahydrothiopyrannyl, methoxytetrahydropyrannyl, 4-methoxy benzyl, phthaloyl, iso-buturyl, isovaleryl, oxalyl, succinyl, pivaloyl, mesyl, para-tert-butyl benzoyl, caprylyl, acryloyl, methyl carbamoyl, phenylcarbamoyl or naphthylcarbamoyl, it being understood that the R" does not represent an alkenyl or alkynyl radical having at most 6 carbon atoms or a linear or branched alkyl radical having at most 6 carbon atoms optionally substituted by one or more radicals chosen from the following radicals, amino, carboxy optionally esterified or salified, alkoxycarbonyl, alkylamino, dialkylamino or heterocyclic aryl when X'-R'a represents an alkoxy, alkylthio or alkenylthio radical, either B] n is not equal to 0, A represents a hydrogen atom, R'1 represents a protector group for the amino radical and either R" represents a -CH2 CO2 H radical or a -C(CH3 )2 CO2 H radical, X' represents an oxygen atom or a sulphur atom and R'a represents a methyl or ethyl radical, or R" represents a  see diagramm : EP0076528,P44,F1 radical, X' represents an oxygen atom or a sulphur atom and R'a represents a methyl radical. 1. Claims for the Contracting State : AT Preparation process of general formula (A') :  see diagramm : EP0076528,P47,F1  syn isomer in which R'1 , R", n, A, X', and R'a have the following significance : either A] represents a hydrogen atom, an equivalent of an alkali metal, of an alkaline-earth metal, of magnesium, of ammonium or of an aminated organic base or A represents the remainder of an ester group that can be easily cleaved, R'a represents an alkyl optionally interrupted by a heteroatom, linear or branched alkenyl or alkynyl radical having at most 6 carbon atoms or a benzyl or phenylethyl radical optionally substituted by a carboxy, amino or dimethylaminoethyl radical, n is equal to 0, 1 or 2, X' represents a sulphur atom optionally oxidised in the form of sulphoxide or sulphone or an oxygen atom and R" and R'1 are such that : either R'1 represents a protector group for the amino radical and R" represents R', R' represents a hydrogen atom, a protector group for the hydroxyl radical, a linear or branched alkyl radical, alkenyl, alkynyl or cycloalkyl radical having at most 6 carbon atoms, or R' represents an acetyl, propionic, butyryl, valeryl, hexanoyl, acryloyl, crotonoyl, benzoyl or carbamoyl radical, each of these radicals being optionally substituted by one or more radicals chosen from the following radicals, carboxy optionally salified or esterified, methoxycarbonyl, ethoxycarbonyl, carbamoyl, dimethylcarbamoyl, amino, methylamino, dimethylamino, halogen, methoxy, ethoxy, propyloxy, methylthio, ethylthiophenyl, tetrazolyl, phenylthio, tetrazolylthio or thiadiazolylthio optionally substituted by methyl or R' represents an alkoxy carbonyl radical, or R'1 represents a hydrogen atom and R" represents a protector group for the hydroxyl radical chosen from the following radicals, phenoxyacetyl, benzoylformyl, p-nitro benzoyl, propoxycarbonyl, beta-beta-beta-trichloroethoxycarbonyl, benzyloxycarbonyl, tert-butoxycarbonyl, 1-cyclopropylethoxycarbonyl, tetrahydropyranyl, tetrahydrothiopyranyl, methoxytetrahydropyranyl, 4-methoxy benzyl, phthaloyl, isobutyryl, isovaleryl, oxalyl, succinyl, pivaloyl, mesyl, para-tert-butyl benzoyl, caprylyl, acryloyl, methyl carbomoyl, phenylcarbomoyl or naphtylcarbomoyl, it being understood that the R" does not represent an alkenyl or alkynyl radical having at most 6 carbon atoms or a linear or branched alkyl radical having at most 6 carbon atoms optionally substituted by one or more radicals chosen from the following radicals, amino, carboxy optionally esterified or salified, alkoxycarbonyl, alkylamino, dialkylamino or heterocyclic aryl when X'-R'a represents an alkoxy, alkylthio or alkenylthio radical ; or B] n is not equal to 0, A represents a hydrogen atom, R'1 represents a protector group for the amino radical and either R" represents a -CH2 CO2 H radical or a -C(CH3 )2 CO2 H radical, X' represents an oxygen atom or a sulphur atom and R'a represents a methyl or ethyl radical or R" represents a  see diagramm : EP0076528,P47,F2  radical, X' represents an oxygen atom or a sulphur atom and R'a represents a methyl radical, characterised in that a product of formula (II')  see diagramm : EP0076528,P47,F3  in which n, X' and R'a have the significance indicated above and A' represents a hydrogen atom or the remainder of an ester group that can be easily eliminated, is treated by a product of formula (IIIA ) :  see diagramm : EP0076528,P48,F1  or a functional derivative of this acid, formula (IIIA ) in which R'1 and R" are as defined above and that the product obtained is optionally esterified or salified.